TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29406	88441;88442;88443	chr2:178556938;178556937;178556936	chr2:179421665;179421664;179421663
N2AB	27765	83518;83519;83520	chr2:178556938;178556937;178556936	chr2:179421665;179421664;179421663
N2A	26838	80737;80738;80739	chr2:178556938;178556937;178556936	chr2:179421665;179421664;179421663
N2B	20341	61246;61247;61248	chr2:178556938;178556937;178556936	chr2:179421665;179421664;179421663
Novex-1	20466	61621;61622;61623	chr2:178556938;178556937;178556936	chr2:179421665;179421664;179421663
Novex-2	20533	61822;61823;61824	chr2:178556938;178556937;178556936	chr2:179421665;179421664;179421663
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAT
• RefSeq wild type template codon: ATA
• Domain: Fn3-102
• Domain position: 72
• Structural Position: 104
• Q(SASA): 0.1064
• Predicted PPI site: N

Reported SAVs

SNV	RS	DUET	PolyPhen-2	Condel	Rhapsody	REVEL	MVP	Source	MAF	Disease	Zygosity	Site annotation	mCSM PPI	Predicted PPI site	Comments	AFR	AMR	AMS	ASJ	EAS	EUR	FIN	MDE	NFE	SAS	OTH
Y/N	None	None	1.0	D	0.859	0.879	0.947828940744	gnomAD-4.0.0	6.84211E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	1.65656E-05

Saturation Mutagenesis

SAV	AlphaMissense (IC)	AlphaMissense Class (IC)	AlphaMissense (N2AB)	AlphaMissense Class (N2AB)	mCSM	mCSM class	PolyPhen-2	PolyPhen-2 Class	Rhapsody	Rhapsody Class	Condel	Condel Score	Site annotation	mCSM PPI	Predicted PPI site
Y/A	0.9695	likely_pathogenic	0.9614	pathogenic	-3.266	Highly Destabilizing	1.0	D	0.832	deleterious	None	None	None	None	N
Y/C	0.7415	likely_pathogenic	0.6757	pathogenic	-2.04	Highly Destabilizing	1.0	D	0.862	deleterious	D	0.673632389	None	None	N
Y/D	0.9798	likely_pathogenic	0.9723	pathogenic	-3.337	Highly Destabilizing	1.0	D	0.855	deleterious	D	0.6991705	None	None	N
Y/E	0.9903	likely_pathogenic	0.9886	pathogenic	-3.125	Highly Destabilizing	1.0	D	0.874	deleterious	None	None	None	None	N
Y/F	0.2643	likely_benign	0.2172	benign	-1.216	Destabilizing	0.999	D	0.727	prob.delet.	D	0.646510203	None	None	N
Y/G	0.9456	likely_pathogenic	0.9341	pathogenic	-3.699	Highly Destabilizing	1.0	D	0.866	deleterious	None	None	None	None	N
Y/H	0.8438	likely_pathogenic	0.8016	pathogenic	-2.223	Highly Destabilizing	1.0	D	0.832	deleterious	D	0.683151139	None	None	N
Y/I	0.9348	likely_pathogenic	0.9196	pathogenic	-1.827	Destabilizing	1.0	D	0.856	deleterious	None	None	None	None	N
Y/K	0.9897	likely_pathogenic	0.9874	pathogenic	-2.286	Highly Destabilizing	1.0	D	0.87	deleterious	None	None	None	None	N
Y/L	0.9141	likely_pathogenic	0.8986	pathogenic	-1.827	Destabilizing	0.999	D	0.8	deleterious	None	None	None	None	N
Y/M	0.942	likely_pathogenic	0.927	pathogenic	-1.637	Destabilizing	1.0	D	0.837	deleterious	None	None	None	None	N
Y/N	0.872	likely_pathogenic	0.8427	pathogenic	-3.051	Highly Destabilizing	1.0	D	0.859	deleterious	D	0.673430584	None	None	N
Y/P	0.9981	likely_pathogenic	0.9978	pathogenic	-2.322	Highly Destabilizing	1.0	D	0.879	deleterious	None	None	None	None	N
Y/Q	0.9775	likely_pathogenic	0.9697	pathogenic	-2.797	Highly Destabilizing	1.0	D	0.844	deleterious	None	None	None	None	N
Y/R	0.975	likely_pathogenic	0.9682	pathogenic	-2.014	Highly Destabilizing	1.0	D	0.864	deleterious	None	None	None	None	N
Y/S	0.9196	likely_pathogenic	0.9056	pathogenic	-3.479	Highly Destabilizing	1.0	D	0.875	deleterious	D	0.6991705	None	None	N
Y/T	0.9633	likely_pathogenic	0.9547	pathogenic	-3.142	Highly Destabilizing	1.0	D	0.874	deleterious	None	None	None	None	N
Y/V	0.8683	likely_pathogenic	0.8506	pathogenic	-2.322	Highly Destabilizing	1.0	D	0.822	deleterious	None	None	None	None	N
Y/W	0.7966	likely_pathogenic	0.7502	pathogenic	-0.465	Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	N

Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.